The goal of the research outlined in the following proposal is to further investigate how neuronal nicotinic receptors are regulated by endogenous and exogenous factors, specifically nerve growth factor and nicotine. Neuronal nicotinic receptors play important roles in both the central and peripheral nervous systems, are implicated in several neruological disorders such as Alzheimer's Disease, and mediate the effects of the addictive drug nicotine. The specific aims of my research are to: (1) investigate how nerve growth factor and nicotine treatment alone and in combination affect neuronal nicotinic receptors in PC 12 cells. I will determine the effects of NGF and nicotine treatment on nicotinic receptor binding sites, function, and subunit protein expression. I will also determine the specific nicotinic receptor subtypes that are regulated by NGF and nicotine. (2) I will determine the mechanisms underlying the regulation of specific receptor populations in PC 12 cells with nicotine and NGF treatment. And (3) I will investigate the effects of nicotine and NGF treatment on native neuronal nicotinic receptors in rat adrenal gland primary cultures. I will then compare these results with those obtained from PC12 cells to determine how will the receptors in PC 12 cells model native tissue.